Lysophosphatidic acid signaling in airway epithelium: role in airway inflammation and remodeling.
Lysophosphatidic acid signaling in airway epithelium: role in airway inflammation and remodeling.
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DOI：
10.1016/j.cellsig.2008.10.010
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发表时间：
2009-03
影响因子：
4.8
通讯作者：
Natarajan V
中科院分区：
文献类型：
--
作者：
Zhao Y;Natarajan V
溶血磷脂酸 (LPA) 是一种有效的生物活性磷脂，可诱导多种细胞反应，包括细胞增殖、迁移和细胞因子释放。 LPA 可以在多种酶的作用下通过多种合成途径在细胞内和细胞外产生，例如磷脂酶 A1/2 (PLA1/2)、磷脂酶 D (PLD)、酰基甘油激酶 (AGK) 和溶血磷脂酶 D (lysoPLD)。 LPA 的代谢受脂质磷酸酶 (LPP) 家族的调节。在各种生物体液中均检测到大量 LPA，包括血清、唾液和支气管肺泡灌洗液 (BALF)。 LPA 最显着的作用似乎是通过激活 G 蛋白偶联受体 (GPCR)（称为 LPA1-6）。 LPA 通过激活多种转录因子来调节基因表达，例如核因子-κB (NF-κB)、AP-1 和 C/EBPβ。除了 GPCR 之外，LPA 受体和受体酪氨酸激酶 (RTK) 之间的串扰也部分调节 LPA 诱导的细胞内信号传导和细胞反应。气道上皮细胞通过释放细胞因子、趋化因子、脂质介质、其他炎症介质以及响应各种吸入刺激而增加屏障功能来参与先天免疫。 LPA 受体的表达已在气道上皮细胞中得到证实。这篇综述总结了我们最近对 LPA / LPA-R 在气道上皮调节中的作用的观察，特别是与促炎和抗炎介质的分泌以及气道屏障功能的调节有关。
Lysophosphatidic acid (LPA), a potent bioactive phospholipid, induces diverse cellular responses, including cell proliferation, migration, and cytokine release. LPA can be generated intracellular and extracellularly through multiple synthetic pathways by action of various enzymes, such as phospholipase A1/2 (PLA1/2), phospholipase D (PLD), acylglycerol kinase (AGK), and lysophospholipase D (lysoPLD). Metabolism of LPA is regulated by a family of lipid phosphate phosphatases (LPPs). Significant amounts of LPA have been detected in various biological fluids, including serum, saliva, and bronchoalveolar lavage fluid (BALF). The most significant effects of LPA appear to be through activation of the G-protein-coupled receptors (GPCRs), termed LPA1-6. LPA regulates gene expression through activation of several transcriptional factors, such as nuclear factor-κB (NF-κB), AP-1, and C/EBPβ. In addition to GPCRs, cross-talk between LPA receptors and receptor tyrosine kinases (RTKs) partly regulates LPA-induced intracellular signaling and cellular responses. Airway epithelial cells participate in innate immunity through the release of cytokines, chemokines, lipid mediators, other inflammatory mediators and an increase in barrier function in response to a variety of inhaled stimuli. Expression of LPA receptors have been demonstrated in airway epithelial cells. This review summarizes our recent observations of the role of LPA / LPA-Rs in regulation of airway epithelium, especially in relation to the secretion of pro- and anti-inflammatory mediators and regulation of airway barrier function.
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